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Beta-glucan ameliorates methotrexate-induced oxidative organ injury via its antioxidant and immunomodulatory effects
Göksel Sener1, Emel Ekşioğlu-Demiralp, Mustafa Cetiner
1Marmara University, School of Pharmacy, Tibbiye Cad. 34668 Istanbul, Turkey. gsener@marmara.edu.tr
Abstract:
Methotrexate is an antifolate that is widely used in the treatment of rheumatic disorders and malignant tumors. The efficacy of methotrexate is often limited by severe side effects and toxic sequelae, where oxidative stress is noticeable. In the present study, the possible protective effect of beta-glucan in methotrexate-induced toxicity was investigated. Following a single dose of methotrexate injection (20 mg/kg), either saline or beta-glucan (50 mg/kg; orally) was administered for 5 days. After decapitation of the rats, trunk blood was obtained and the ileum, liver and kidney were removed to measure tissue malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity and collagen content, as well as histological examination. Methotrexate caused a significant decrease in GSH levels, while MDA levels, MPO activity and collagen content were increased in all the tissues (P<0.05-0.001). On the other hand, administration of beta-glucan following methotrexate abolished the depletion of GSH and inhibited the increases in MDA, MPO activity and collagen content, while the histological analysis revealed that beta-glucan attenuated the tissue damage. Stimulation index, an indicator of oxidative burst in the neutrophils, was decreased by methotrexate (P<0.001), while beta-glucan abolished this effect. Furthermore, increased leukocyte apoptosis and cell death in methotrexate-treated animals were inhibited by beta-glucan (P<0.05). Thus, the findings of the present study suggest that beta-glucan, through its antioxidant and immunoregulatory effects, may be of therapeutic value in alleviating the leukocyte apoptosis, oxidative tissue injury and thereby the intestinal and hepatorenal side effects of methotrexate treatment.
Insights
Beta-glucan may protect against methotrexate toxicity by reducing oxidative stress and inflammation. This study found beta-glucan mitigated methotrexate-induced damage in rats, suggesting therapeutic potential.
Area of Science:
- Pharmacology and Toxicology
- Immunology
- Biochemistry
Background:
- Methotrexate (MTX) is a crucial antifolate drug for rheumatic diseases and cancers.
- MTX efficacy is often compromised by severe side effects, including oxidative stress.
- Understanding protective agents against MTX toxicity is clinically significant.
Purpose of the Study:
- To investigate the potential protective effects of beta-glucan against methotrexate-induced toxicity.
- To evaluate beta-glucan's impact on oxidative stress markers and tissue damage.
- To assess beta-glucan's influence on immune cell responses.
Main Methods:
- Rats received a single dose of methotrexate (20 mg/kg) followed by saline or beta-glucan (50 mg/kg) orally for 5 days.
- Tissues (ileum, liver, kidney) and blood were analyzed for malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO) activity, and collagen.
- Histological examination, leukocyte apoptosis, and neutrophil oxidative burst (stimulation index) were assessed.
Main Results:
- Methotrexate significantly depleted GSH and increased MDA, MPO activity, and collagen content in tissues.
- Beta-glucan administration reversed GSH depletion and inhibited increases in MDA, MPO activity, and collagen.
- Beta-glucan attenuated MTX-induced tissue damage, reduced leukocyte apoptosis, and normalized neutrophil oxidative burst.
Conclusions:
- Beta-glucan demonstrates significant antioxidant and immunoregulatory properties.
- Beta-glucan may alleviate methotrexate-induced leukocyte apoptosis and oxidative tissue injury.
- Beta-glucan shows therapeutic potential in mitigating intestinal, liver, and kidney side effects of methotrexate.
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